1. Field of the Invention
The present invention relates to substituted cyclopentene compounds of the general formula I, to a process for the production thereof, to pharmaceutical preparations containing these compounds and to the use thereof for the production of pharmaceutical preparations.
2. Brief Description of Related Developments
The neuropeptide α-CGRP (α-calcitonin gene-related peptide) consisting of 37 amino acids arises by alternative splicing of the calcitonin gene. Another CGRP, β-CGRP, is furthermore known, which exhibits elevated sequence analogy with α-CGRP, but is transcribed from another gene.
These neuropeptides are stored in or released from the nerve ends of the central and peripheral nervous system and exert their physiological action by binding to specific G-protein-coupled receptors known as CGRP receptors. These CGRP receptors, various subtypes of which such as CGRP1 and CGRP2 are known, are located on the surface of cells of various tissues, such as for example muscle cells, glandular cells, epithelial cells or neuronal cells.
Given the widespread distribution of CGRP receptors in tissues of various specialisations, the CGRP peptide receptor system is of central significance in numerous physiological and pathophysiological processes, such as for example processes of the cardiovascular system, of the central and/or peripheral nervous system, of the respiratory system or of the endocrine system. For example, patients with acute migraine and those with cluster headaches have a plasma concentration of the neuropeptide CGRP which is higher than that of a healthy comparison group.
The regulation of CGRP receptors, in particular the inhibition of CGRP receptors with the assistance of a receptor-specific antagonist, accordingly opens up a new approach for the successful treatment of disorders and diseases associated with the CGRP ligand-receptor system.
The object of the present invention was accordingly to provide novel compounds which are in particular suitable as pharmaceutical active ingredients in pharmaceutical preparations. These compounds should preferably be suitable for regulating the CGRP receptor, in particular as an antagonist for the inhibition of CGRP receptors. These compounds should likewise preferably be suitable for the treatment and/or prevention of disorders and/or diseases, which are at least partially mediated by the CGRP receptor, preferably by the CGRP-1 receptor, for the prevention and/or treatment of pain, preferably of acute pain, chronic pain, chronic inflammatory pain and/or visceral pain, cluster headaches, neurovascular disorders, migraine, preferably of migraine with aura, migraine without aura, common migraine, classic migraine or complicated migraine, inflammation, preferably pulmonary inflammation, asthma, arthritis, hypertonia, hypotonia, tachycardia, non-insulin-dependent diabetes mellitus, cardiovascular diseases, skin conditions and/or skin damage, preferably skin damage caused by heat and/or radiation, particularly preferably skin damage caused by sunburn, allergic rhinitis, diseases which accompany overshooting vascular dilation, preferably shock or sepsis, menopausal hot flushes or opioid tolerance, preferably morphine tolerance.
It has surprisingly now been found that the substituted cyclopentene compounds according to the invention of the general formula I below exhibit an elevated affinity for the CGRP receptor and are suitable as antagonists, in particular for the inhibition of the CGRP receptor, preferably of the CGRP1 receptor.